NT-pro BNP and plasma-soluble ST2 as promising biomarkers for hypertension, hypertensive heart disease and heart failure in sub-Saharan Africa.

Dear Sir In three recent publications, Ojji and colleagues reported on the role of two novel biomarkers, NT-pro-BNP and plasma soluble ST2, for differentiating sub-Saharan African people with hypertension (HT) without left ventricular hypertrophy (LVH) and without heart failure (HF) from hypertensive people with LVH (HTLVH) and those with HF (HTHF). The authors clinically and echocardiographically evaluated a group of 210 patients with hypertension residing in Abuja, the capital city of Nigeria. All these patients had measurements done for the cardiac neurohormone NT-pro-BNP and for soluble ST2, which is a novel cardiac biomarker of mechanical strain. In the first publication, in which they investigated the effect of LV remodelling on the concentration of soluble ST2, the authors found that subjects with HTHF had higher plasma ST2 concentrations compared to those with HTLVH and those with HT (134.7 ± 57.3 vs 23.0 ± 8.3 vs 14.5 ± 4.9 ng/ml, all p < 0.0001). Soluble ST2 also had a strong correlation with clinical and echocardiographic parameters. The authors concluded that ‘Plasma ST2 is a useful biomarker in not only differentiating HTHF from HT with or without LVH, but also distinguishes hypertensive LVH from HT without LVH’. In the second publication, the authors investigated the relationship between soluble ST2 levels and LV geometric patterns in the same cohort of patients with HT and found that patients with concentric LVH had higher soluble ST2 levels compared with patients with normal LV geometry (20.4 ± 8.4 vs 14.3 ± 5.4 ng/ml, p < 0.002). This also led to the conclusion that ‘soluble ST2 level is not only affected by hypertensive LVH, but may be a future biomarker in differentiating concentric hypertrophy from normal geometry in hypertension’. In the third study, the authors examined the effect of NT-proBNP on LV and RV remodelling in this same hypertensive African cohort. Participants with HTHF had significantly higher NT-pro-BNP levels compared to those with HTLVH. Based on these results, the authors proposed that NT-pro-BNP could be a useful biomarker for differentiating HT with or without LVH from HTHF in black hypertensive subjects. The conclusions drawn by these authors are valid exclusively in the study context for a number of reasons. First, it is important to remember that hypertension and hypertensive heart disease, which are potentially preventable diseases, are the main contributors of the growing burden of heart failure in SSA. Second, echocardiography is globally the cornerstone of the routine assessment of various types of hypertensive heart disease as it allows for the detection of normal left ventricular concentric remodelling, concentric versus eccentric LVH, and HF with the possible differentiation between HF with reduced ejection fraction and HF with preserved ejection fraction using tissue Doppler imaging, as well as the measurement of pulmonary artery pressure, another prognostic marker in this population. However, echocardiography remains expensive, less available in most SSA settings, and requires experts both for its performance and interpretation. For these reasons, requesting cardiac echocardiography in most settings in SSA is like searching for the goose that lays the golden egg. There is value therefore in using circulating biomarkers, which could be useful as surrogate markers of the heart disease process in resource-poor settings. Natriuretic peptide (BNP and NT-proBNP) levels have been shown to accurately reflect left ventricular pressure, and studies have found that peptide levels are sensitive and specific for diagnosing heart failure and also relevant for risk stratification. There is no doubt that the third study by Ojji et al. is a confirmation of the usefulness of the diagnostic role of NT-pro BNP in the SSA setting and it has immediate relevance for clinicians. Contrary to NT-pro BNP measurement, which is already an established gold standard for HF, soluble ST2 as a biomarker has been less investigated. Just as with other novel biomarkers, such as mid-regional pro-atrial natriuretic peptide (MR-proANP) and galectin-3, which are promising diagnostic and prognostic biomarkers beyond established natriuretic peptides, the role of soluble ST2 in the clinical care of patients is yet to be established beyond any doubt. It is very encouraging to note that, as suggested by Ojji and co-workers, soluble ST2 can help differentiate HT, HTLVH and HTHF, as well as concentric LVH from normal LV geometry. The relevance of these three studies by Ojji and co-workers in this particular context should however not completely Department of Medicine, University of Cape Town, Cape Town, South Africa; Douala General Hospital and Clinical Research Education Networking and Consultancy, Douala, Cameroon; Faculty of Health Sciences, University of Buea, Buea, Cameroon Anastase Dzudie, MD, aitdzudie@yahoo.com


Dear Sir
In three recent publications, [1][2][3] Ojji and colleagues reported on the role of two novel biomarkers, NT-pro-BNP and plasma soluble ST2, for differentiating sub-Saharan African people with hypertension (HT) without left ventricular hypertrophy (LVH) and without heart failure (HF) from hypertensive people with LVH (HTLVH) and those with HF (HTHF). The authors clinically and echocardiographically evaluated a group of 210 patients with hypertension residing in Abuja, the capital city of Nigeria. All these patients had measurements done for the cardiac neurohormone NT-pro-BNP and for soluble ST2, which is a novel cardiac biomarker of mechanical strain.
In the first publication, 1 in which they investigated the effect of LV remodelling on the concentration of soluble ST2, the authors found that subjects with HTHF had higher plasma ST2 concentrations compared to those with HTLVH and those with HT (134.7 ± 57.3 vs 23.0 ± 8.3 vs 14.5 ± 4.9 ng/ml, all p < 0.0001). Soluble ST2 also had a strong correlation with clinical and echocardiographic parameters. The authors concluded that 'Plasma ST2 is a useful biomarker in not only differentiating HTHF from HT with or without LVH, but also distinguishes hypertensive LVH from HT without LVH'.
In the second publication, 2 the authors investigated the relationship between soluble ST2 levels and LV geometric patterns in the same cohort of patients with HT and found that patients with concentric LVH had higher soluble ST2 levels compared with patients with normal LV geometry (20.4 ± 8.4 vs 14.3 ± 5.4 ng/ml, p < 0.002). This also led to the conclusion that 'soluble ST2 level is not only affected by hypertensive LVH, but may be a future biomarker in differentiating concentric hypertrophy from normal geometry in hypertension'.
In the third study, 3 the authors examined the effect of NT-pro-BNP on LV and RV remodelling in this same hypertensive African cohort. Participants with HTHF had significantly higher NT-pro-BNP levels compared to those with HTLVH. Based on these results, the authors proposed that NT-pro-BNP could be a useful biomarker for differentiating HT with or without LVH from HTHF in black hypertensive subjects.
The conclusions drawn by these authors are valid exclusively in the study context for a number of reasons. First, it is important to remember that hypertension and hypertensive heart disease, which are potentially preventable diseases, are the main contributors of the growing burden of heart failure in SSA. 4 Second, echocardiography is globally the cornerstone of the routine assessment of various types of hypertensive heart disease as it allows for the detection of normal left ventricular concentric remodelling, concentric versus eccentric LVH, and HF with the possible differentiation between HF with reduced ejection fraction and HF with preserved ejection fraction using tissue Doppler imaging, as well as the measurement of pulmonary artery pressure, another prognostic marker in this population. 5 However, echocardiography remains expensive, less available in most SSA settings, and requires experts both for its performance and interpretation. For these reasons, requesting cardiac echocardiography in most settings in SSA is like searching for the goose that lays the golden egg.
There is value therefore in using circulating biomarkers, which could be useful as surrogate markers of the heart disease process in resource-poor settings. Natriuretic peptide (BNP and NT-pro-BNP) levels have been shown to accurately reflect left ventricular pressure, and studies have found that peptide levels are sensitive and specific for diagnosing heart failure and also relevant for risk stratification. 6,7 There is no doubt that the third study by Ojji et al. 3 is a confirmation of the usefulness of the diagnostic role of NT-pro BNP in the SSA setting and it has immediate relevance for clinicians.
Contrary to NT-pro BNP measurement, which is already an established gold standard for HF, soluble ST2 as a biomarker has been less investigated. Just as with other novel biomarkers, such as mid-regional pro-atrial natriuretic peptide (MR-proANP) and galectin-3, which are promising diagnostic and prognostic biomarkers beyond established natriuretic peptides, the role of soluble ST2 in the clinical care of patients is yet to be established beyond any doubt. It is very encouraging to note that, as suggested by Ojji and co-workers, soluble ST2 can help differentiate HT, HTLVH and HTHF, as well as concentric LVH from normal LV geometry.
The relevance of these three studies by Ojji and co-workers in this particular context should however not completely overshadow the shortcomings. First, this was a single-centre study with a limited number of participants. Second, heart disease and especially heart failure in this population may have included cases of different severity and chronicity, especially ischaemic causes, which could limit the generalisability of their findings to all hypertensive patients. Finally, further research is required to determine the optimal cut-off points for diagnosis, the relevance of serial measurements, changes following treatment, and the prognostic role in Africans, before they can be widely recommended for clinical decision making.

Statins associated with improved heart structure and function
Statins are associated with improved heart structure and function, according to research presented recently at EuroCMR 2017. The benefits were above and beyond the cholesterol-lowering effect of statins. 'Statins are primarily used to lower cholesterol', said lead author Dr Nay Aung, a cardiologist and Wellcome Trust research fellow, William Harvey Research Institute, Queen Mary University of London, UK. 'They are highly effective in preventing cardiovascular events in patients who have had a heart attack or are at risk of heart disease.' He continued: 'Statins have other beneficial, non-cholesterollowering, effects. They can improve the function of the blood vessels, reduce inflammation, and stabilise fatty plaques in the blood vessels. Studies in mice and small studies in humans have shown that statins also reduce the thickness of heart muscle but this needed to be confirmed in a larger study.' This study investigated the association between statins and heart structure and function. The study included 4 622 people without cardiovascular disease from the UK Biobank, a large community-based cohort study. Cardiac magnetic resonance imaging was used to measure left and right ventricular volumes and left ventricular mass. Information on statin use was obtained from medical records and a selfreporting questionnaire.
The relationship between statin use and heart structure and function was assessed using a statistical technique called multiple regression, which adjusts for potential confounders that can have an effect on the heart, such as ethnicity, gender, age, and body mass index (BMI).
Nearly 17% of participants were taking statins. Those taking statins were older, had higher BMI and blood pressure, and were more likely to have diabetes and hypertension. 'This was not surprising because we prescribe statins to patients at high risk of heart disease and these are all known risk factors', said Dr Aung.
Patients taking statins had a 2.4% lower left ventricular mass and lower left and right ventricular volumes. Dr Aung said: 'People using statins were less likely to have a thickened heart muscle (left ventricular hypertrophy) and less likely to have a large heart chamber. Having a thick, large heart is a strong predictor of future heart attack, heart failure or stroke and taking statins appears to reverse the negative changes in the heart which, in turn, could lower the risk of adverse outcomes. ' 'It is important to note that in our study, the people taking statins were at higher risk of having heart problems than those not using statins yet they still had positive heart remodelling compared to the healthier control group', added Dr Aung.
In terms of how statins might reduce the thickness and volume of the heart, Dr Aung said several studies have demonstrated that statins reduce oxidative stress and dampen the production of growth factors that stimulate cell growth. Statins also increase the production of nitric oxide by the cells lining the blood vessels, leading to vasodilatation, improved blood flow, lower blood pressure, and lower stress on the heart, which is less likely to become hypertrophied.
The findings raise the issue of extending statin prescriptions to anyone above the age of 40 years, but Dr Aung said that was probably not the way to go.
'There are clear guidelines on who should receive statins', he said. 'There is debate about whether we should lower the bar and the question is when do you stop. What we found is that for patients already taking statins, there are beneficial effects beyond cholesterol lowering and that's a good thing. But instead of a blanket prescription, we need to identify people most likely to benefit, that is, personalised medicine.' Dr Aung said: 'A dual approach should be considered to identify people who will benefit most from statins. That means looking at not only clinical risk factors, such as smoking and high blood pressure, but also genetic (hereditary) factors, which can predict individuals' response to statins. This is an area of growing interest and one that we are also investigating in our lab with our collaborators.'